1. Technical Field
The invention relates to methods and materials involved in protein kinase C iota signaling. The invention also relates to transgenic animals, inhibitors of protein kinase C iota signaling, methods for inhibiting protein kinase C iota signaling, methods for identifying inhibitors of protein kinase C iota signaling, and methods for diagnosing cancer.
2. Background Information
Protein kinase C iota (PKC iota or PKCι) plays a requisite role in Bcr-Abl mediated resistance to chemotherapy-induced apoptosis (Jamieson et al., J. Biol. Chem., 274:3927-3930 (1999) and Murray et al., J. Biol. Chem., 272:27521-4 (1997)), and is critical for epithelial cell polarity (Suzuki et al., J. Cell Sci., 115:3565-73 (2002)) and cell survival (Jamieson et al., J. Biol. Chem., 274:3927-3930 (1999) and Murray et al., J. Biol. Chem., 272:27521-4 (1997)). PKCι has also been implicated in Ras-mediated signaling (Coghlan et al., Mol. Cell. Biol., 20:2880-9 (2000); Kampfer et al, J. Biol. Chem., 276:42834-42 (2001); and Uberall et al 1., J. Cell Biol., 144:413-25 (1999)). Activating Ras mutations occur in about 30 percent of all human cancers (Adjei, J. Natl. Cancer Inst., 93:1062-74 (2001)), and in about 50 percent of human colon adenomas and carcinomas (Bos, Cancer Res., 49:4682-9 (1989)). Ras mutations are an early event in colon carcinogenesis and are often present in preneoplastic lesions in the colon (Pretlow et al., J. Natl. Cancer Inst., 85:2004-7 (1993) and Zaidi et al, Carcinogenesis., 16:451-6 (1995)).